Chronic iron overload induces functional and structural vascular changes in small resistance arteries via NADPH oxidase-dependent O2− production

Blockade of angiotensin AT1 receptors prevents arterial remodelling and stiffening in iron‐overloaded rats

“…Thus, a direct cause–effect relationship between iron per se and arterial stiffness has not yet been clinically established, as all trials were conducted in individuals with co‐morbidities that were not controlled. In animal models, Wistar male rats, after 4 weeks of iron‐overload, exhibited functional, structural, and mechanical changes in mesenteric resistance arteries, accompanied by an increase in the aortic PWV (Ribeiro Júnior et al, ). There was evidence of inward hypertrophic remodelling associated with increased collagen deposition in the small arteries, which could be responsible for enhancing vascular stiffness due to iron‐overload.…”

“…In the present study, we found that after 2 weeks of iron‐dextran injections using a double‐dose, there was increased aortic PWV, but unchanged BP and vascular tone control. This could be intriguing because increasing evidence indicates that chronic iron‐overload is associated with endothelial dysfunction (Bertoli et al, ; Day et al, ; Marques et al, ; Ribeiro Júnior et al, ). However, in our present study, we assessed vascular structure and function at 15 days of iron‐overload, and, according to both in vivo and in vitro protocols, there was no impairment of the vascular tone control and endothelium, and NO modulations were preserved as well.…”

“…injections of iron dextran at 200 mg·kg −1 , 5 days a week for 2 weeks, while the control group received saline isotonic solution for the same period and the same enforcement regime as the iron group. The parenteral administration of iron dextran in rats has been used by our group (Bertoli et al, ; Marques et al, ; Ribeiro Júnior et al, ) and others (El‐Sheikh, Ameen, & AbdEl‐Fatah, ; Gong et al, ; Ishizaka et al, ; Lou et al, ), and it has been shown to be an appropriate model that mimics clinical situations of iron‐overload such as haemosiderosis or haemochromatosis. In addition, in a second set of experiments, to evaluate the effect of AT 1 receptor blockade on the aortic mechanics during iron‐overload, another sample of rats were randomized into four groups: control, iron‐overload, control treated with losartan, or iron‐overload treated with losartan.…”

“…In this regard, we identified that, in the rat model of iron‐overloading, there is an impairment of the vascular function associated with increased production of ROS and reduced NO bioavailability in conductance (Marques et al, ) and resistance arteries (Bertoli et al, ; Ribeiro Júnior, Marques, Nunes, Stefanon, & dos Santos, ). These studies also suggested that vascular dysfunction induced by iron‐overload may be a result of localized changes in angiotensin II (Ang II), as in vitro blockade of the angiotensin AT 1 receptors reversed functional changes (Bertoli et al, ; Marques et al, ).…”

“…These studies also suggested that vascular dysfunction induced by iron‐overload may be a result of localized changes in angiotensin II (Ang II), as in vitro blockade of the angiotensin AT 1 receptors reversed functional changes (Bertoli et al, ; Marques et al, ). Moreover, Ribeiro Júnior et al () demonstrated that chronic iron‐overload induces not only functional but also structural changes in the artery characterized by vascular remodelling, collagen deposition, and increased aortic pulse wave velocity (PWV).…”